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Antifungal Activity of Sodium Bicarbonate Against Fungal Agents Causing Superficial Infections
Abstract
Although sodium bicarbonate-NaHCO(3) (SB) has many domestic and medical, traditional and empirical uses, only little scientific documentation of its activity is available. The aims of this study were to investigate the antifungal activity of SB on the three fungal groups (yeasts, dermatophytes and molds) responsible for human skin and nail infections. We first evaluated the in vitro antifungal activity of SB on 70 fungal strains isolated from skin and nail infections: 40 dermatophytes, 18 yeasts and 12 molds. A concentration of 10 g/L SB inhibited the growth of 80 % of all the fungal isolates tested on Sabouraud dextrose agar. The minimal inhibitory concentration 90 (MIC90) of SB measured on Sabouraud dextrose agar, Sabouraud dextrose broth and potato dextrose broth was 5 g/L for the yeasts, 20 g/L for the dermatophytes and 40 g/L for the molds. In a second step, we prospectively evaluated the ex vivo antifungal activity of SB on 24 infected (15 dermatophytes, 7 yeasts and 2 molds) clinical specimens (15 nails and 9 skin scrapings). The fungal growth was completely inhibited for 19 (79 %) specimens and reduced for 4 (17 %) specimens after 7 days of incubation on Sabouraud dextrose-chloramphenicol agar supplemented with 10 g/L of SB as compared to Sabouraud dextrose-chloramphenicol agar without SB. In conclusion, we documented the antifungal activity of SB on the most common agents of cutaneous fungal infection and onychomycosis, and we specified the effective concentrations for the different groups of pathogenic fungi. The mechanism of action of SB has yet to be explored.
... mm) could curb the growth of 80% of these pathogens. The effectiveness varies based on the type of fungi, with a minimum inhibitory concentration (MIC 90 ) against yeast of 59.52 mm, dermatophytes requiring 238.10 mm, and moulds needing up to 476.19 mm [24]. Furthermore, when tested against clinical isolates, HCO 3 -(119.05 ...
... Furthermore, when tested against clinical isolates, HCO 3 -(119.05 mm) completely stopped the growth of 19 out of 24 samples and notably reduced the growth of the remaining samples within a week compared with samples without HCO 3 - [24]. These findings suggest that HCO 3 can be used in combination with other antifungal agents, particularly for skin fungal infections and onychomycosis. ...
HCO3– is involved in pH homoeostasis and plays a multifaceted role in human health. HCO3– has been recognized for its antimicrobial properties and is pivotal in bacterial antibiotic susceptibility. Notably, the interconversion between CO2 and HCO3–, facilitated by the enzyme carbonic anhydrase (CA), is crucial in tissues infected by pathogens. Studies have highlighted the antimicrobial potency of CA inhibitors, emphasizing the importance of this enzyme in this area. The potential of HCO3– as an antibiotic adjuvant is evident; its ability to increase virulence in pathogens such as Enterococcus faecalis and Mycobacterium tuberculosis requires meticulous scrutiny. HCO3– modulates bacterial behaviours in diverse manners: it promotes Escherichia coli O157:H7 colonization in the human gut by altering specific gene expression and, with Pseudomonas aeruginosa, amplifies the effect of tobramycin on planktonic cells while promoting biofilm formation. These multifaceted effects necessitate profound mechanistic exploration before HCO3– can be considered a promising clinical adjuvant.
... The efficient treatment of fungal infections is particularly difficult since fungal cell structure and metabolism are similar to those of eukaryotic hosts. Recently, the scientists have focused on the potential antimicrobial effects of certain natural products, which have the advantage of being readily available, environmentally friendly, and low in toxicity [16,29]. ...
... Antifungal activities of sodium bicarbonate and potassium carbonate have already been demonstrated [16,23,24,27]. Several studies suggest that disturbance of internal homeostasis of potassium and sodium cations is responsible for a growth arrest of the cell [3,15]. ...
Cutaneous fungal infections are common and widespread. Antifungal agents used for the treatment of these infections often have undesirable side effects. Furthermore, increased resistance of the microorganisms to the antifungal drugs becomes the growing problem. Accordingly, the search for natural antifungal compounds continues to receive attention. Apoptosis is highly regulated programmed cell death. During yeast cell apoptosis, amino acids and peptides are released and can stimulate regeneration of human epithelium cells. Thus, detection of chemical compounds inducing apoptosis in yeast and nontoxic for humans is of great medical relevance. The aim of this study was to detect chemical compound inducing apoptosis in pathogenic Candida species with the lowest toxicity to the mammalian cells. Five chemical compounds-acetic acid, sodium bicarbonate, potassium carbonate, lithium acetate, and formic acid-were tested for evaluation of antifungal activity on C. albicans, C. guilliermondii, and C. lusitaniae. The results showed that acetic acid and formic acid at the lowest concentrations induced yeast cells death. Apoptosis analysis revealed that cells death was accompanied by activation of caspase. Minimal inhibitory concentrations of potassium carbonate and sodium bicarbonate induced Candida cells necrosis. Toxicity test with mammalian cell cultures showed that formic acid has the lowest effect on the growth of Jurkat and NIH 3T3 cells. In conclusion, our results show that a low concentration of formic acid induces apoptosis-like programmed cell death in the Candida yeast and has a minimal effect on the survivability of mammalian cells, suggesting potential applications in the treatment of these infections.
... Salicylic acid acts as a plant hormone, triggering defense responses in plants, inducing the expression of genes involved in plant immunity, leading to the production of antimicrobial compounds (Spoel & Dong, 2024), and can also directly inhibit fungal growth by interfering with cell wall synthesis, membrane integrity, and metabolic processes. In addition, sodium bicarbonate creates an alkaline environment that is unfavourable for fungal growth, disrupting the fungal cell's osmoregulation, leading to dehydration and cell death (Bru et al., 2013). This compound induces the production of ROS that damages the fungal cells. ...
... A decrease in the hue angle (h) and luminosity (L*) values is associated with the senescence process, as the color changes from green to yellow due to the degradation is more favorable to completely disrupt germination. At higher concentrations of 2 and 3%, increased osmotic stress could induce cellular responses that partially mitigate fungal inhibition [27]. Smilanick et al. [14] reported inhibition of germination of P. digitatum spores by the application of acetic acid, peracetic acid, and hydrogen peroxide in citrus degreening room. ...
The application of generally recognized as safe (GRAS) substances for postharvest fungal control of fruit is an alternative to the conventional use of synthetic fungicides. In this study, two GRAS compounds were applied by ultrasonic nebulization (USN) to lime fruit for the control of Penicillium italicum, the cause of blue mold. Lime fruits were treated with sodium bicarbonate (1, 2, 3% w/v), acetic acid (0.5, 1, 1.5% w/v) and sterile distilled water by USN for 5, 10–15 min. The effect of the USN treatments was evaluated in vitro, selecting the agent with the best effect. In vivo, the incidence and severity of blue mold disease and lime fruit quality parameters were evaluated. Although sodium bicarbonate inhibited P. italicum in vitro tests, USN treatments with acetic acid significantly inhibited 75.4% of mycelial growth and 100% of P. italicum germination. USN treatments (1% and 1.5% acetic acid) reduced disease incidence and severity (preventive and curative tests) on fruit stored at 25 °C; however, at 15 °C there was no significant difference with respect to USN of sterile distilled water. Lime quality parameters were not adversely affected by USN treatments with acetic acid. The application of 1 or 1.5% acetic acid by USN appears to be a promising option for the control of blue mold disease in Persian lime fruits.
... For the most common human fungus, Candida albicans, work with carbonate has examined two mycosis scenarios. A 5% sodium bicarbonate solution reduced adhesion of C. albicans cells to denture material (acrylic resin) (Sousa et al. 2009) and elevated carbonate levels inhibited the growth of clinical isolates from foot onychomycosis or cutaneous fungal infection (Letscher-Bru et al. 2013). Growth of C. albicans on implanted medical devices, such as vascular catheters, pacemakers, and artificial heart valves, is a serious problem (Kojic and Darouiche 2004;Hashemi Fesharaki et al. 2018;Glowacki, Quraishi, and Zakhireh 1990) and additional options for preventing or reducing growth on these surfaces are required. ...
Candida albicans, a member of the normal microbial population of healthy humans, is an opportunistic pathogen that can cause serious disease in immunocompromised patients. An important virulence factor of C. albicans is the formation of biofilms. These organized communities of cells are efficient at attaching to host cells and implanted medical devices. Carbonate has been studied as an agricultural antifungal agent, and here we demonstrate that carbonate can affect filamentation, biofilm formation, and antifungal drug resistance in C. albicans.
... The IC 50 represented the concentration of the Caraway EO or carvone at which 50 % inhibition of fungal growth was observed. IC 50 values were calculated using nonlinear regression analysis with statistical software (Letscher-Bru et al., 2013;Bocate et al., 2019). ...
Introduction: Currently available antifungal therapies often have limitations such as toxicity and the development of resistance. The aim of this study was to investigate the antifungal activity and mode of action of Caraway (Carum carvi L.) essential oil (EO) and its constituent carvone against A. fumigatus, a fungal pathogen responsible for invasive aspergillosis. Methods: Caraway EO was obtained by hydrodistillation, and its antifungal activity was assessed by the broth microdilution method according to the CLSI protocol. The ergosterol content of fungal mycelia was measured using a spectrophotometric method. The mode of action of Caraway EO was assessed by electron microscopy. The interaction between Caraway EO and two known antifungals, itraconazole and caspofungin, was evaluated by determining the fractional inhibitory concentration index (FICI). Results: At twofold dilutions ranging from 3.12 to 400 mg/mL, Caraway EO inhibited A. fumigatus growth by 10.27À100 %, with a minimum inhibitory concentration (MIC) of 200 mg/mL, while carvone inhibited fungal growth by 7.31À67.58 %, with an MIC of 400 mg/mL. The IC 50 values of the Caraway EO and carvone were 56.09 and 47.68 mg/mL, respectively. Moreover, the minimum fungicidal concentration (MFC) of the Caraway EO was reported to be 400 mg/mL. Both Caraway EO and carvone significantly inhibited ergosterol biosynthesis in A. fumigatus. Caraway EO showed synergistic antifungal activity in combination with itraconazole (FICI=0.38) and additive antifungal activity (FICI=0.75) in combination with caspofungin. Conclusion: Caraway EO and its constituent carvone showed strong antifungal activity against A. fumiga-tus by inhibiting ergosterol biosynthesis and destroying essential compartments of fungal mycelia, such as mitochondria. In addition, the combination of carvone with itraconazole or caspofungin had syner-gistic/additive effects, suggesting potential therapeutic efficacy for the treatment of A. fumigatus-related infections.
... The therapeutic properties of sodium bicarbonate have been studied to demonstrate its effectiveness against skin pathologies due to its antimicrobial and anti-pruritic properties. A study from a French group suggested that sodium bicarbonate has antimicrobial effects, particularly antifungal activity [96]. ...
Atopic dermatitis is a chronic inflammatory skin disease. The treatment plays an important role in influencing the patients’ quality of life. The basic management consists of appropriate skin cleansing, including bathing and eventually using bathing additives. Recommendations regarding frequency and duration of bathing, water temperature and usefulness of bathing additives are widely different, often leading to confusion among patients. This review aims to give insights into the best bathing practices and the use of bathing additives in atopic dermatitis in children. Several bathing additives, including bleach baths, commercial baby cleansers, bath baby oils and bath salt, appear to be promising adjunctive therapies for atopic dermatitis due to their anti-inflammatory, anti-bacterial, anti-pruritus and skin barrier repair properties through different mechanisms of action. However, their efficacy and safety are not fully understood in some cases. The usefulness of other bath additives, such as acidic and more natural substances (green tea extracts, pine tar, sodium bicarbonate), is still under investigation. Further studies are needed to determine their optimal use to achieve clinical benefit safely.
... NaHCO 3 was effective in reducing phytotoxicity through neutralization reactions. Furthermore, NaHCO 3 is already being used as an alternative fungicide in plant gardening [30,31] and has no adverse effects on humans and the environment (Fact sheet, EPA). Therefore, although it was not tried in the field in this study, pre-treatment with NaHCO 3 has the potential to be used as an EF-phytotoxicity mitigation agent for higher target CT values. ...
Background
Ethyl formate (EF) is naturally occurring volatile compound used as quarantine fumigant for pest control. Recently, conversion of uses of EF was tried from quarantine to agricultural field due to its promising efficacy. However, there is a lack of studies on the residue pattern on crops and soil and the phytotoxic mechanism of EF in greenhouse environment. This study aimed to evaluate the efficacy, residue analysis, and phytotoxicity of EF fumigation in controlling Myzus persicae and Thrips palmi , on cucurbit crops and establish an optimized fumigation strategy for use in greenhouses.
Results
The results showed that EF was more effective against M. persicae than against T. palmi. Residue analysis indicated that EF rapidly decomposed and was not retained after 30 min in leaves and 2 h in soil after fumigation, suggesting the potential for residue-free pest control. Phytotoxicity test revealed that watermelon was the most sensitive crop to EF, and H 2 O 2 accumulation was observed above a concentration of 7.5 g/m ³ . A strategy to reduce phytotoxicity with sodium bicarbonate during fumigation showed promising results in reducing phytotoxic effects on the crops. The optimized EF fumigation with 6 g/m ³ was applied in a greenhouse, resulting in 100% and 40% mortality of M. persicae and T. palmi , respectively, with no notable phytotoxicity and EF residue in the treated crops and soil.
Conclusion
This study demonstrates that optimized EF fumigation can be an environmentally sustainable method for controlling pests in greenhouses, paving the way for improved pest management practices and sustainable agriculture. Further research is needed to validate these findings and explore the potential of EF fumigation for other crops and pests.
Graphical Abstract
... 베이킹 소다를 농산물에 처리한 연구 사례는 파파야 (Gamagae et al., 2003), 체리 (Karabulut et al., 2001) (Yao et al., 2004;Palou et al., 2009;Letscher-Bru et al., 2013 ...
... The acidic nasal pH is known to increase the availability of free iron, which might lead to fungal growth. 14,15 So, adding sodium bicarbonate could modulate the nasal pH and potentially mitigate the growth of Mucor sps. Kim et al. showed that a low-concentration HClO could be used against a spectrum of organisms, including a Rhizopus oryzae; their cell-line-based research demonstrated substantial neutralization. ...
... growth, protect the ulcer surface, reduce saliva viscosity, and neutralize oral acidity, promoting OM healing (34). It should be noted that we could not conclude which mouthwash was best among sodium bicarbonate, GM-CSF, and povidone-iodine after two weeks of treatment because comparative data on GM-CSF and povidone-iodine were lacking. ...
Background
Oral mucositis (OM) is one of the most common adverse effects of radiotherapy and chemotherapy. It greatly affects the patients' quality of life and hinders cancer treatment implementation. Treating OM with mouthwash is a widely used strategy that can effectively relieve symptoms and promote healing. However, the wide mouthwash selection confuses clinicians. This Bayesian network meta-analysis aimed to compare the effects of various mouthwash types used to treat OM and provide high-level evidence-based recommendations for OM treatment.
Methods
Database search included PubMed, Embase, Cochrane Library, and Web of Science from inception to April 21, 2022. The primary outcome was OM score improvement following the World Health Organization grades. The randomized controlled trial (RCT) bias risk assessment tool provided in the Cochrane Handbook assessed the studies' risk of bias. We performed pairwise and Bayesian network meta-analysis with random effects following the PRISMA guideline.
Results
The study included 13 RCTs with 570 patients. Pairwise comparisons showed that povidone-iodine was more effective than chlorhexidine (weighted mean difference [WMD], −2.64; 95% confidence interval [CI], −2.72 to −2.56) but inferior to granulocyte-macrophage colony-stimulating factor (GM-CSF; WMD, 0.20; 95% CI, 0.06–0.34) after one week of mouthwash treatment. Vitamin E (WMD, −0.94; 95% CI, −1.03 to −0.85), natural drugs (WMD, −0.93; 95% CI, −1.46 to −0.40), and phenytoin (WMD, −0.38; 95% CI, −0.59 to −0.17) exhibited better therapeutic effects than a placebo after three weeks of treatment. Bayesian network meta-analysis showed that povidone-iodine was superior to chlorhexidine in treating OM (WMD, 2.63; 95% CI, 0.20–5.01). Other mouthwashes showed no significant differences. Rank probability indicated that the best OM therapeutic mouthwashes were GM-CSF (54%), vitamin E (24%), and natural drugs (43%) after one, two, and three weeks of treatment, respectively.
Conclusion
GM-CSF was the most effective mouthwash type for OM treatment. When considering the cost and effectiveness, povidone-iodine and sodium bicarbonate might be the most advantageous. Furthermore, natural drugs have the same potential in treating OM. Safety and acceptability are their most outstanding characteristic.
... For example, the combine use of live yeast and NaHCO 3 for dietary feed additives in domestic animals (Galip, 2006;Marden et al., 2008). NaHCO 3 inhibits the production of pathogenic toxins and enhances biocontrol efficacy of antagonistic yeasts on postharvest fungal diseases (Samapundo et al., 2007;Geng et al., 2011;Letscher-Bru et al., 2013;Zhang et al., 2020). NaHCO 3 is also widely used to formulate toothpaste, mouthwashes, and cosmetic products. ...
Sodium bicarbonate (NaHCO3) is an important inorganic salt. It is not only widely used in industrial production and daily life, but is also the main stress in alkaline saline soil. NaHCO3 has a strong ability to inhibit the growth of fungi in both natural environment and daily application. However, the mechanism by which fungi respond to NaHCO3 stress is not fully understood. To further clarify the toxic mechanisms of NaHCO3 stress and identify the specific cellular genes and pathways involved in NaHCO3 resistance, we performed genome-wide screening with NaHCO3 using a Saccharomyces cerevisiae deletion mutant library. A total of 33 deletion mutants with NaHCO3 sensitivity were identified. Compared with wild-type strains, these mutants had significant growth defects in the medium containing NaHCO3. Bioinformatics analysis found that the corresponding genes of these mutants are mainly enriched in the cell cycle, mitophagy, cell wall integrity, and signaling pathways. Further study using transcriptomic analysis showed that 309 upregulated and 233 downregulated genes were only responded to NaHCO3 stress, when compared with yeast transcriptomic data under alkaline and saline stress. Upregulated genes were mainly concentrated in amino acid metabolism, steroid biosynthesis, and cell wall, while downregulated genes were enriched in various cellular metabolisms. In summary, we have identified the cellular pathways and key genes that respond to NaHCO3 stress in the whole genome, providing resource and direction for understanding NaHCO3 toxicity and cellular resistance mechanisms.
... campestris, as it is already a substance studied for the control of several phytopathogenic fungi and has the purpose of increasing the fruit preservation period, besides being easily accessible and inexpensive when compared to other GRAS substances (Bru et al., 2013;Lai et al., 2015;Fallanaj et al., 2016). ...
The conventional methods used for angular stain control are generally chemical methods, however the use of these products can cause high environmental impact and damage to consumer health if it is used in large quantities and undiluted and applied correctly. Based on this problem, this work aimed to evaluate in vitro alternative forms of control using Saccharomyces yeast (with probiotic potential), ethanolic extracts of Mauritia flexuosa (Buriti) and Miconia albicans (Cinnamon-old) plants. To evaluate four GRAS substances in angular leaf spot control caused by Xanthomonas campestris pv. Mangifera indica, during the postharvest period in mangoes. In vitro results using antagonist yeasts showed no inhibitory effect against X. campestris. However, the extracts of the plants Miconia albicans and Mauritia flexuosa showed a significant inhibition. Thus, as two GRAS substances, 1%, 1.5% and 3% sodium carbonate and 3% sodium bicarbonate inhibited X. campestris growth 100%. Given the results obtained, the plant extracts and the GRAS substances tested were effective in controlling phytobacteria and proved to be an alternative in controlling angular leaf spot, thus avoiding economic losses during the mango postharvest phase.
... Sodium bicarbonate has been used for many years as a common and nontoxic household item and is an additive to foods and dental products. While it has been reported to inhibit the growth of fungi (56,57) and bacteria including Streptococcus mutans (58), its antibacterial and antivirulence properties have not been fully exploited to date. In an agricultural setting, bicarbonate can be delivered as an ammonium or potassium salt, rather than sodium, with similar effects on PMF (42). ...
... Sodium bicarbonate has been used for many years as a common and nontoxic household item and is an additive to foods and dental products. While it has been reported to inhibit the growth of fungi (56,57) and bacteria including Streptococcus mutans (58), its antibacterial and antivirulence properties have not been fully exploited to date. In an agricultural setting, bicarbonate can be delivered as an ammonium or potassium salt, rather than sodium, with similar effects on PMF (42). ...
... Sodium bicarbonate has been used for many years as a common and nontoxic household item and is an additive to foods and dental products. While it has been reported to inhibit the growth of fungi (56,57) and bacteria including Streptococcus mutans (58), its antibacterial and antivirulence properties have not been fully exploited to date. In an agricultural setting, bicarbonate can be delivered as an ammonium or potassium salt, rather than sodium, with similar effects on PMF (42). ...
Rice is an important source of food for more than half the world’s population. Bacterial panicle blight (BPB) is a disease of rice characterized by grain discoloration or sheath rot caused mainly by Burkholderia glumae . B. glumae synthesizes toxoflavin, an essential virulence factor, that is required for symptoms of the disease. The products of the tox operons, ToxABCDE and ToxFGHI, are responsible for the synthesis and the proton motive force (PMF)-dependent secretion of toxoflavin, respectively. The DedA family is a highly conserved membrane protein family found in most bacterial genomes that likely function as membrane transporters. Our previous work has demonstrated that absence of certain DedA family members results in pleiotropic effects, impacting multiple pathways that are energized by PMF. We have demonstrated that a member of the DedA family from Burkholderia thailandensis , named DbcA, is required for the extreme polymyxin resistance observed in this organism. B. glumae encodes a homolog of DbcA with 73% amino acid identity to Burkholderia thailandensis DbcA. Here, we created and characterized a B. glumae Δ dbcA strain. In addition to polymyxin sensitivity, B. glumae Δ dbcA is compromised for virulence in several BPB infection models and secretes only low amounts of toxoflavin (∼15% of wild type levels). Changes in membrane potential in B. glumae Δ dbcA were reproduced in the wild type strain by the addition of sub-inhibitory concentrations of sodium bicarbonate, previously demonstrated to cause disruption of PMF. Sodium bicarbonate inhibited B. glumae virulence in rice suggesting a possible non-toxic chemical intervention for bacterial panicle blight.
IMPORTANCE
Bacterial panicle blight (BPB) is a disease of rice characterized by grain discoloration or sheath rot caused mainly by Burkholderia glumae . The DedA family is a highly conserved membrane protein family found in most bacterial genomes that likely function as membrane transporters. Here, we constructed a B. glumae mutant with a deletion in a DedA family member named dbcA and report a loss of virulence in models of BPB. Physiological analysis of the mutant shows that the proton motive force is disrupted, leading to reduction of secretion of the essential virulence factor toxoflavin. The mutant phenotypes are reproduced in the virulent wild type strain without an effect on growth using sodium bicarbonate, a nontoxic buffer that has been reported to disrupt the PMF. The results presented here suggest that bicarbonate may be an effective antivirulence agent capable of controlling BPB without imposing an undue burden on the environment.
... These inhibitory effects were observed following both 6-and 17-h incubations, indicating that bacterial growth was hampered both in exponential and stationary phases. These findings are in accordance with previous observations demonstrating the antimicrobial effects of NaHCO 3 [19,[31][32][33]. Corral and colleagues reported that 120 mM NaHCO 3 reduces the CFU counts of E. coli, L. plantarum, S. aureus and P. aeruginosa 10,000-fold. ...
Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene encoding an epithelial anion channel. In CF, Cl⁻ and HCO3⁻ hyposecretion, together with mucin hypersecretion, leads to airway dehydration and production of viscous mucus. This habitat is ideal for colonization by pathogenic bacteria. We have recently demonstrated that HCO3⁻ inhibits the growth and biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus when tested in laboratory culture media. Using the same bacteria our aim was to investigate the effects of HCO3⁻ in artificial sputum medium (ASM), whose composition resembles CF mucus. Control ASM containing no NaHCO3 was incubated in ambient air (pH 7.4 or 8.0). ASM containing NaHCO3 (25 and 100 mM) was incubated in 5% CO2 (pH 7.4 and 8.0, respectively). Viable P. aeruginosa and S. aureus cells were counted by colony-forming unit assay and flow cytometry after 6 h and 17 h of incubation. Biofilm formation was assessed after 48 h. The data show that HCO3⁻ significantly decreased viable cell counts and biofilm formation in a concentration-dependent manner. These effects were due neither to extracellular alkalinization nor to altered osmolarity. These results show that HCO3⁻ exerts direct antibacterial and antibiofilm effects on prevalent CF bacteria.
... To date, most of the reported chemicals that claim to have potential antifungal functions have a high MIC. However, these antifungal agents usually have a strong resistance reversal potential in FLZresistant C. albicans (Letscher-Bru et al., 2013;Padmavathi et al., 2015). Therefore, it may be necessary to find a new drug that can increase the antifungal activity of FLZ as another method to expand the antifungal library (Guo et al., 2008). ...
Here, we aim to investigate the antifungal effect and mechanism of action of sodium new houttuyfonate (SNH) against Candida albicans. Microdilution analysis results showed that SNH possesses potent inhibitory activity against C. albicans SC5314, with a MIC80 of 256 μg/mL. Furthermore, we found that SNH can effectively inhibit the initial adhesion of C. albicans. Inverted microscopy, crystal violet staining, scanning electron microscopy and confocal laser scanning microscopy results showed that morphological changes during the transition from yeast to hypha and the biofilm formation of C. albicans are repressed by SNH treatment. We also found that SNH can effectively inhibit the biofilm formation of clinical C. albicans strains (Z103, Z3044, Z1402, and Z1407) and SNH in combination with fluconazole, berberine chloride, caspofungin and itraconazole antifungal agents can synergistically inhibit the biofilm formation of C. albicans. Eukaryotic transcriptome sequencing and qRT-PCR results showed that SNH treatment resulted in significantly down-regulated expression in several biofilm formation related genes in the Ras1-cAMP-Efg1 pathway (ALS1, ALA1, ALS3, EAP1, RAS1, EFG1, HWP1, and TEC1) and significantly up-regulated expression in yeast form-associated genes (YWP1 and RHD1). We also found that SNH can effectively reduce the production of key messenger cAMP in the Ras1-cAMP-Efg1 pathway. Furthermore, using Galleria mellonella as an in vivo model we found that SNH can effectively treat C. albicans infection in vivo. Our presented results suggest that SNH exhibits potential antibiofilm effects related to inhibiting the Ras1-cAMP-Efg1 pathway in the biofilm formation of C. albicans.
... Even though AST of fungi uses RPMI-1640 liquid medium, a mammalian cell culture medium, this is buffered to pH 7.0 with MOPS (CLSI, 2017a,c), rather than sodium bicarbonate as it would be when culturing mammalian cells and using a CO 2 incubator (5% CO 2 ). Sodium bicarbonate has antibacterial, antifungal and antibiofilm properties of its own, but only at supra-physiological concentrations (≥50 mM) (Corral et al., 1988;Xie et al., 2010;Letscher-Bru et al., 2013;Dobay et al., 2018;Farha et al., 2018). Bicarbonate acts as a selective dissipater of the trans-membrane pH gradient, a component of the proton motive force (along with the membrane potential) and can enhance the activity of AMP, including LL-37, α-defensin, indolicidin, protegrin and bactenecin and selected antibiotics, including aminoglycosides, macrolides and selected fluoroquinolones. ...
During the development of antimicrobial peptides (AMP) as potential therapeutics, antimicrobial susceptibility testing (AST) stands as an essential part of the process in identification and optimisation of candidate AMP. Standard methods for AST, developed almost 60 years ago for testing conventional antibiotics, are not necessarily fit for purpose when it comes to determining the susceptibility of microorganisms to AMP. Without careful consideration of the parameters comprising AST there is a risk of failing to identify novel antimicrobials at a time when antimicrobial resistance (AMR) is leading the planet toward a post-antibiotic era. More physiologically/clinically relevant AST will allow better determination of the preclinical activity of drug candidates and allow the identification of lead compounds. An important consideration is the efficacy of AMP in biological matrices replicating sites of infection, e.g., blood/plasma/serum, lung bronchiolar lavage fluid/sputum, urine, biofilms, etc., as this will likely be more predictive of clinical efficacy. Additionally, specific AST for different target microorganisms may help to better predict efficacy of AMP in specific infections. In this manuscript, we describe what we believe are the key considerations for AST of AMP and hope that this information can better guide the preclinical development of AMP toward becoming a new generation of urgently needed antimicrobials.
... [9, 14,15] Accordingly, candida culture suspension (100 µl) was platted on Sabouraud dextrose agar plates and incubated for 30 min. various potencies of the selected homoeopathic medicines (20 µl) were added in wells (3 mm dia.) made on the agar. ...
... SB is widely used in medicine to treat numerous diseases, with several applications in the field of internal medicine; in fact, its efficacy when used on a topical basis has been demonstrated in many studies, for instance in treatment of gingivitis [16], oral hygiene protection [17], as well as associated with paracetamol in pharyngitis and in interstitial cystitis [18,19]. In vitro antimicrobial efficacy against microorganisms such as dermatophytes (Candida albicans, Escherichia coli, Staphylococcus aureus , group B streptococci) has also been studied [20,21]. However, for treatment of psoriasis, the only form of SB whose effectiveness has been demonstrated is balneotherapy. ...
Introduction
Psoriasis is a chronic inflammatory disease characterized by the presence of erythematosquamous lesions. A wide variety of topical treatments for therapy of this pathology are available, including sodium bicarbonate (SB). A few papers reported in literature focus on use of SB baths for treatment of psoriasis, but none assess evidence concerning the efficacy of SB topical preparations. This study aimed to determine the effectiveness of a galenic SB in lanette vax formulation compared with lanette vax base in mild to moderate stable plaque psoriasis.
Methods
A randomized, double-blind, intrapatient, controlled study was performed in 28 days. Thirty patients of both genders were selected for testing. A blinded investigator evaluated the patients’ psoriasis using a modified Psoriasis Area and Severity Index (PASI), body surface area (BSA), and objective parameters using sensors (Multiprobe Adapter MPA5; Courage & Khazaka Electronic GmbH, Cologne, Germany).
Results
Data analysis of objective parameters highlighted that use of the SB topical preparation led to no improvement in skin hydration, no reduction in transepidermal water loss, and no decrease of erythema. The modified PASI and BSA did not change from baseline.
Conclusions
The results obtained show that use of the studied product did not improve psoriatic lesions.
... Richards and Mcbride (1971) used the sodium bicarbonate as a preservative of eye lotion against the contamination with Pseudomonas aeruginosa. Letscher-Bru et al. (2013), documented the effect of sodium bicarbonate against the most common strains of fungi affecting the skin and nails in human. There were several studies that reported the germicidal or the antimicrobial effect of boric acid in different tissue other than the eye. ...
here are numerous agents that have been used for irrigation of the ocular tissue from attached foreign bodies, inflammatory exudate and microorganisms. For evaluation of four agents of these irrigation solutions, sixteen clinically healthy dogs of both sexes were used in this study. The dogs were allocated into four equal groups. The right eye of dogs for each group was irrigated 3 times daily for three successive days. The groups were irrigated as following: The first group: ringer’s lactate, the second group: normal saline 0.9%, the third group: boric acid 2% and sodium bicarbonate 1% was used for the fourth group. The left eye was considered control one. The results revealed that the four solutions did not cause any obvious alteration of the eyes and change the intraocular pressure (IOP). According to their effects on the total bacterial count, the four irrigation solutions had not any significant effect. It could be concluded that all of these agents may be used for irrigation of the intact eye and removal of the attached exudate and foreign bodies.
... Aside from a few herbal drugs showing relatively low MIC alone (such as berberine and sodium houttuyfonate ≤64 µg/mL), the anti-Candida effect is relatively weak in a majority of plant drugs (usually MIC > 256 µg/mL). The case is also not changed for other non-conventional antifungal agents which are converted to antifungal purpose (Zhou et al., 2012;da Silva et al., 2013;Letscher-Bru et al., 2013;Shahzad et al., 2014). To strengthen the efficacy of individual drug for antifungal usage and traditional antimycotics in the treatment of Candida resistant strains, the The initial inoculum was newly prepared at 1 × 10 6 CFU/mL. ...
Fungal infections caused by Candida albicans and non-albicans Candida [NAC] species are becoming a growing threat in immunodeficient population, people with long-term antibiotic treatment and patients enduring kinds of catheter intervention. The resistance to one or more than one conventional antifungal agents contributes greatly to the widespread propagation of Candida infections. The severity of fungal infection requires the discovery of novel antimycotics and the extensive application of combination strategy. In this study, a group of Candida standard and clinical strains including C. albicans as well as several NAC species were employed to evaluate the antifungal potentials of palmatine (PAL) alone and in combination with fluconazole (FLC)/itraconazole (ITR) by microdilution method, checkerboard assay, gram staining, spot assay, and rhodamine 6G efflux test. Subsequently, the expressions of transporter-related genes, namely CDR1, CDR2, MDR1, and FLU1 for C. albicans, CDR1 and MDR1 for Candida tropicalis and Candida parapsilosis, ABC1 and ABC2 for Candida krusei, CDR1, CDR2, and SNQ2 for Candida glabrata were analyzed by qRT-PCR. The susceptibility test showed that PAL presented strong synergism with FLC and ITR with fractional inhibitory concentration index (FICI) in a range of 0.0049–0.75 for PAL+FLC and 0.0059–0.3125 for PAL+ITR in planktonic cells, 0.125–0.375 for PAL+FLC and 0.0938–0.3125 for PAL+ITR in biofilms. The susceptibility results were also confirmed by gram staining and spot assay. After combinations, a vast quantity of rhodamine 6G could not be pumped out as considerably intracellular red fluorescence was accumulated. Meanwhile, the expressions of efflux-associated genes were evaluated and presented varying degrees of inhibition. These results indicated that PAL was a decent antifungal synergist to promote the antifungal efficacy of azoles (such as FLC and ITR), and the underlying antifungal mechanism might be linked with the inhibition of efflux pumps and the elevation of intracellular drug content.
... Regarding sodium bicarbonate, there is strong evidence in the literature of its antifungal activity for both filamentous fungi and yeast causing mycoses in humans. The literature indicates that solutions of sodium bicarbonate in concentrations of 5 g/L and 20-40 g/L are effective for the elimination, respectively, of yeasts and filamentous fungi (Letscher-Bru et al. 2013). ...
This quantitative and qualitative study aimed to evaluate the level of fungal contamination in computer keyboards from an Integrated Health Center (IHC) at Piauí, Brazil, and to evaluate the efficacy of 50% sodium bicarbonate and 50% alcoholic vinegar solutions to eliminate these microorganisms. Ten keyboards from six sectors of the IHC were chosen randomly, and the collection was performed in three situations: (i) before of disinfection, (ii) after disinfection with solution of sodium bicarbonate, and (iii) after disinfection with solution of alcoholic vinegar. Samples were inoculated in Petri dishes with dextrose agar potato plus chloramphenicol and incubated at room temperature for 72 h. All keyboards were contaminated with opportunistic fungi, with Cladosporium cladosporioides (29.4%) being the most frequent species, followed by Curvularia lunata (17.6%) and Aspergillus niger, Alternaria alternata, and Curvularia clavata with 11.8% each. The two solutions were proven to be efficient in eliminating fungal contamination; however, the sodium bicarbonate solution caused esthetic damages in keyboards. In addition, this study is the first report of the antifungal activity of alcoholic vinegar in filamentous fungi. Based on our findings, we suggest a daily disinfection of keyboards with a 50% vinegar solution plus adequate hygiene from the hands of professionals before and after the use of the computer and its annexes, as key actions to reduce nosocomial infections, particularly in economically disadvantaged countries.
... accuracy and reproducibility of our assay. Studies on fungal growth usually omit sodium bicarbonate because it causes growth inhibition of many fungal species (18). We observed that Malassezia spp. ...
Malassezia is a genus of lipid dependent yeasts. It is associated with common skin diseases such as pityriasis versicolor or atopic dermatitis and can cause systemic infections in immunocompromised individuals. Owing to slow growth and lipid requirements of these fastidious yeasts, convenient and reliable antifungal drug susceptibility testing assays for Malassezia spp. are not widely available. We have therefore optimized a broth microdilution assay for the testing of Malassezia that is based on the assays from CLSI and EUCAST for Candida and other yeasts. The addition of ingredients such as lipids and esculin provided a broth medium formulation, which enabled the growth of all Malassezia spp. and could be read with the colorimetric indicator resazurin by visual and by fluorescence reading. We have tested the susceptibility of 52 strains of 13 species of Malassezia against 11 commonly used antifungals. MIC values determined by visual reading were in good agreement with MIC values determined by fluorescence reading. The lowest MICs were found for the azoles itraconazole, posaconazole and voriconazole with MIC90 values of 0.03-1.0 μg/ml, 0.06-0.5 μg/ml and 0.03-2.0 μg/ml, respectively. All Malassezia spp. were resistant to echinocandins and griseofulvin. Some Malassezia spp. also showed high MIC values for ketoconazole, which is the most widely recommended topical antifungal to treat Malassezia skin infections. In summary, our assay enables the fast and reliable susceptibility testing of Malassezia spp. against a large panel of different antifungals.
... As a consequence of increased abuse of traditional antifungal agents and antibiotics, the ever-increasing rate of resistance of C. albicans, especially to fluconazole poses a serious threat to antifungal therapy, calling for urgent need in search of novel antifungal drugs. To date, most of the reported chemicals claimed to possess potential antimycotic functions have relatively high minimum inhibitory concentrations (MICs); however, these antifungals usually had strong potential of resistance reversion in fluconazole-resistant C. albicans (Quan et al. 2006;Zhou et al. 2012;Letscher-Bru et al. 2013;Padmavathi et al. 2015). Therefore, finding new drugs capable of improving the antifungal activity of fluconazole can be taken into account as an alternative way to expand the antifungal bank (Guo et al. 2008). ...
Context: Fluconazole resistance is an intractable problem of treating Candida albicans, calling for more antifungal agents to enhance the activity of fluconazole.
Objective: This work investigates the anti-C. albicans activities of sodium houttuyfonate (SH) and/or fluconazole and the associated mechanism.
Materials and methods: The minimum inhibitory concentrations (MICs) of SH and fluconazole both ranging from 0.5 to 1024 μg/mL were determined by broth microdilution method in 19 C. albicans isolates, and their fractional inhibitory concentration index (FICI) was evaluated by checkerboard assay. After MICSH and/or MICfluconazole treatments, the expressions of IFD6, PHR1, ZAP1, ADH5, BGL2, XOG1 and FKS1 were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans 1601.
Results and conclusion: The MICs of SH alone ranged from 32 to 256 μg/mL and decreased 2–16-fold in combination. SH showed strong synergism with fluconazole with FICI <0.13–0.5. In C. albicans 1601, we observed that (i) the expression of the seven genes increased notably in a range between 3.71- and 12.63-fold (p < 0.05) when SH was used alone, (ii) the combined use of SH and fluconazole slightly inhibited the expression of IFD6 and PHR1 by 1.23- and 1.35-fold (p > 0.05), but promoted evidently the expression of ZAP1, ADH5, XOG1 and FKS1 by 1.98-, 3.56-, 4.10- and 2.86-fold (p < 0.05). The results suggested SH to be a potential synergist to enhance the antifungal activity of fluconazole in C. albicans resistant isolates, and the underlying mechanism may be associated with β-1,3-glucan synthesis and transportation.
... Therefore, the search for novel effective agents to reverse the resistance of fluconazole-resistant C. albicans becomes urgent. Many traditional antioxidant, antiinflammatory, and antibacterial agents have been considered to have favorable antifungal potential alone and/ or in combination with FLC against fluconazole-resistant C. albicans (Zhou et al. 2012;Letscher-Bru et al. 2013). ...
Context:
Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species.
Objective:
This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism.
Materials and methods:
The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003.
Results:
For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 μg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed.
Discussion and conclusion:
Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.
... Несмотря на то что местная терапия онихомикозов в ряде клинических ситуаций не является полностью оправданным терапевтическим подходом, есть целый ряд исследований, которые направлены именно на изучение препаратов, потенциально эффективных в качестве топической терапии онихомикозов [33][34][35][36]. Наряду с инновационными лекарственными формами уже существующих обусловленным дрожжевыми патогенами (следует помнить о высокой вторичной резистентности C. glabrata и природной устойчивости C. krusei), тогда как при дерматомикозах, вызванных дерматомицетами, возможен риск неэффективности терапии. ...
Onychomycosis is a fungal infection of nails of fingers of the hands or feet, resulting in thinning, and the subsequent destruction, discoloration and desquamation of the nail plate from the nail bed. The etiology of onychomycosis in most cases are dermatomycetes, Candida species and non-dermatomycetes filamentous fungi. The prevalence of onychomycosis in the general population is high and varies in different countries. Current approaches to the therapy include the use of systemic therapy, which is the main therapeutic approach, topical (local) therapy, administered to a specific group of patients and a number of non-drug treatments. When using any of the therapy the achieving of high clinical efficacy is a difficult task. The main problem is the inability to create sufficient concentrations of the active substance in the structure of the nail unit. At present, there is research data regarding a new drug compounds and the novel representatives of existing classes of antimycotics. One of the potential approaches to the treatment of onychomycosis may be the use of drugs, leading to a decrease in pH in the nail tissue and inhibition of the growth of fungi. This article provides general information about the epidemiology, etiology and pathogenesis of onychomycosis, and also a data on pharmacology and clinical studies of the new combined preparation for the therapy of onychomycosis will be presented for the first time.
Fungi occurred naturally like Candida yeast, in the human body. It may grow on skin, inside the digestive system and vagina. Antifungal drugs are used to kill or stop this fungal growth. According to their mode of action they are divided into azoles (inhibit ergosterol synthesis), echinocandins (damage cell walls), and polyenes (destroy fungal cells) etc. Depending on the seriousness of infection and type of infection, generally antifungal drugs are administered to a body. Oral antifungals are taken by mouth for systemic infections. Topical antifungals (creams, ointments) treat localized skin and nail infections. Intravenous (IV) administration is used for severe cases. Common side effects of antifungals are yeast infection, hepatotoxicity, ringworm, nail and skin infections etc. Serious fungal infections pose a growing threat to human health specially for vulnerable patients having significant morbidity and mortality such as AIDS patients, transplant recipients, and individuals using certain medications. Some of the existing antifungal drugs, particularly azoles, are facing increasing resistance. In order to ensure successful treatment of these drug-resistant infections, there is a critical need for the development of novel antifungal agents which is very challenging. Here about the antifungals, its classification, pros and cons of using antifungal drugs, prevention and control of antifungals are discussed in detail.
Background
One important complication of the coronavirus disease 2019 (COVID-19) is COVID Associated Mucormycosis (CAM), especially in patients with conditions such as diabetes and in immunosuppressed patients. Systemic acidosis, hyperglycemia, and other biochemical factors such as free iron and β-hydroxybutyrate (BHB) can play a role in this complication.
Materials and Methods
Rhizopus oryzae was isolated from a patient at Masih Daneshvari Hospital microbiology laboratory and sub-cultured on the Potato Dextrose Agar (PDA) for 48 hours at 37 °C. Subsequently, Roswell Park Memorial Institute (RPMI) 1640 Broth medium buffered to pH 7.0 with 3-N-morpholino-propane sulfonic acid. Macrodilution and microdilution methods were performed with 8.4% sodium bicarbonate. After 24 hours of incubation at 35°C, the minimum inhibitory concentration (MIC) and the minimum fungicidal concentrations (MFC) were evaluated.
Results
We found that the minimum inhibitory and fungicidal concentrations are at 1.05 % and 2.1 % respectively. Therefore, the minimum concentration is 2% sodium bicarbonate, which requires achieving the desired environmental pH for fungal inhibition and fungicidal effects.
Conclusion
Regulation of systemic acidosis by sodium bicarbonate could be used to decrease the chance of mucormycosis. In addition, According to our study and some others, an alkaline environment can prevent fungal growth. We found that a minimum concentration of 2% sodium bicarbonate is required to achieve the desired mucosal pH to inhibit the fungus. Therefore, sodium bicarbonate inhalation, as a cost-effective and well-tolerated medicine, is a good candidate for the prevention of mucormycosis. In this regard, extensive clinical and laboratory research is needed to achieve more accurate doses and appropriate administration intervals.
The cyanobacterium strain Synechococcus cedrorum SAG 88.79 stock culture has fungal contamination stated by the Sammlung von Algenkulturen der Universität Göttingen itself. In this recent work, this particular fungal strain was isolated, identified, and morphologically characterised. The fungal strain AGSC12 belongs to the species Cyphellophora olivacea, with respect to the sequence similarity, phylogeny, and morphology of the strain. Colony morphology and growth capability were examined on SMA, EMMA, PDA, MEA, YEA, and YPA plates. Growth of the colonies was the most successful on YPA plates, followed by PDA and MEA containing plates. Surprisingly, the AGSC12 strain showed extreme tolerance to NaHCO3, albeit it, is is considered a general fungistatic compound. Moreover, positive association between the AGSC12 and SAG 88.79 strains was revealed, as the SAG 88.79 strain always attained higher cell density in co-cultures with the fungus than in mono-cultures. Besides, a taxonomic note on the SAG 88.79 strain itself was also stated.
Hispidin is a secondary metabolite with pharmacological properties that is produced by the medicinal mushroom Phellinus linteus. In this study, we evaluated the effect of metal ion addition to grain media while determining the optimal illumination and temperature conditions for hispidin production in P. linteus 03 using solid-state fermentation. Six metal ions were added to these media and P. linteus 03 grown in these media were for hispidin production under optimal incubation temperature and illumination conditions. The highest yield and specific productivity of hispidin, and total hispidin content were achieved at 25 °C in a dark environment which was maintained throughout the entire fermentation period for brown rice and pearl barley media. Addition of Zn²⁺ ions to brown rice medium resulted in the highest yield and specific productivity of hispidin and total hispidin content at 6 weeks of fermentation; these were 2.53-, 2.62-, and 2.43-fold, respectively higher than those observed in the control. This study shows that hispidin production by P. linteus 03 can be enhanced by the addition of Zn²⁺ ions to the grain media.
Candida glabrata infections are responsible for deaths of people globally. Fluconazole is
known to be less effective against C. glabrata, which developed many strategies to evade being
destroyed by fluconazole. To achieve enhanced efficacy of fluconazole against C. glabrata, the
interaction of fluconazole with sodium bicarbonate was investigated using the CLSI guidelines.
The efficacy of fluconazole alone and in combination with sodium bicarbonate was evaluated
using the time-kill and phospholipase production assays. Eventually, the expression of PLB was
assessed using semi-quantitative RT-PCR to investigate the inhibitory properties of fluconazole
alone and in combination with sodium bicarbonate against C. glabrata. The fluconazole/sodium
bicarbonate combination displayed synergistic and antagonistic effects (FICI= 0.375-4.25).
In C. glabrata ATCC, SN 152, and SN 164, the fluconazole/sodium bicarbonate combination
exhibited a significant fungicidal activity (p<0.05) but antagonistic effect in the case of SN
283. With exception of SN 283, a significant reduction was noted in phospholipase production
in clinical isolates of C. glabrata treated with fluconazole/sodium bicarbonate combination.
The PLB was down-regulated significantly by 0.168-0.515 fold in C. glabrata treated with
fluconazole/sodium bicarbonate. The results suggested fluconazole/sodium bicarbonate to
have a potential synergistic interaction in C. glabrata, and the underlying mechanism may be
associated with phospholipase gene.
The antibacterial properties of sodium bicarbonate have been known for years, yet the molecular understanding of its mechanism of action is still lacking. Utilizing chemical-chemical combinations, we first explored the effect of bicarbonate on the activity of conventional antibiotics to infer on mechanism. Remarkably, the activity of 8 classes of antibiotics differed in the presence of this ubiquitous buffer. These interactions and a study of mechanism of action revealed that, at physiological concentrations, bicarbonate is a selective dissipater of the pH gradient of the proton motive force across the cytoplasmic membrane of both Gram-negative and Gram-positive bacteria. Further, while components that make up innate immunity have been extensively studied, a link to bicarbonate, the dominant buffer in the extracellular fluid, has never been made. Here, we also explored the effects of bicarbonate on components of innate immunity. Although the immune response and the buffering system have distinct functions in the body, we posit there is interplay between these, as the antimicrobial properties of several components of innate immunity were enhanced by a physiological concentration of bicarbonate. Our findings implicate bicarbonate as an overlooked potentiator of host immunity in the defense against pathogens. Overall, the unique mechanism of action of bicarbonate has far-reaching and predictable effects on the activity of innate immune components and antibiotics. We conclude that bicarbonate has remarkable power as an antibiotic adjuvant and suggest that there is great potential to exploit this activity in the discovery and development of new antibacterial drugs by leveraging testing paradigms that better reflect the physiological concentration of bicarbonate.
Penicillium expansum, a widespread filamentous fungus, is a major causative agent of fruit decay and may lead to the production of patulin which causes harmful effects on human health. In this study, P. expansum isolated from naturally infected pears (Pyrus bretschneideri Rehd.) was identified by morphological observation and rDNA-internal transcribed spacer analysis. Then, the effects of exogenous sodium bicarbonate (NaHCO3) on development and pathogenicity of P. expansum were evaluated in vitro and in vivo. Results indicated that NaHCO3 at 0.6% (w/v) significantly (P < 0.05) reduced the germination of P. expansum conidia by up to 80% compared to the control after 10 h incubation. NaHCO3 also showed good ability to inhibit germ tube elongation, mycelia expansion and hypha production of P. expansum. The lesion diameter and disease incidence of blue molds were markedly reduced by 0.6% NaHCO3 treatment. Loss of membrane integrity was examined and quantified under 0.6% NaHCO3 condition by the method of propidium iodide fluorescent staining. Furthermore, we found that NaHCO3 obviously affected the relative expressions of four genes involved in patulin biosynthesis and effectively prevented patulin accumulation. These data will provide theoretical foundations for improving the application potential of NaHCO3 on postharvest horticulture pathogens control.
Unlabelled:
Growth of enteropathogenic Escherichia coli E2348/69 was inhibited by bicarbonate in a dose-dependent manner, showing approximately 5% growth reduction at 5 mmol l(-1) while kanamycin at 3·12 μg ml(-1) inhibited growth by 15%, yet when kanamycin and bicarbonate were combined at these concentrations, inhibition increased to 80%. Unexpectedly, at bicarbonate concentrations >20 mmol l(-1) enhancement of the antibiotic activity virtually disappeared, i.e. there was a paradoxical Eagle-like effect. How bicarbonate acts is unclear, but neutral or alkaline pH also enhanced the activity of kanamycin. However, several differences indicated a separate effect of bicarbonate. First, bicarbonate inhibited growth more than the corresponding increments in pH. Second, at low concentration, the antibiotic enhancing effect of bicarbonate was stronger than the effect of pH alone. Third, 5 mmol l(-1) bicarbonate significantly enhanced the activity of kanamycin while the corresponding pH had no effect. Fourth, the Eagle-like effect was exclusive of bicarbonate because changes in pH did not induce an analogous behaviour. Notwithstanding the mechanism, the enhancing effect of bicarbonate was indubitable. Consequently, it seems worthwhile to explore further its potential to improve the efficacy of aminoglycosides and maybe even other antibiotics.
Significance and impact of the study:
Bicarbonate at a low concentration enhanced the in vitro antibiotic activity of kanamycin and gentamicin. Even though the action mechanism of bicarbonate is hitherto unknown, it seems worthwhile to explore further its capacity to improve the efficacy of aminoglycosides. Clearly, the well-known harmful side-effects of aminoglycosides are a concern. However, it has recently been shown in a fish model that bicarbonate may protect ciliary cells against the damage caused by aminoglycosides. So, it seems possible that bicarbonate could help reduce aminoglycoside dosage at the same time that it might help lessen the damage to auditory ciliary cells in humans.
Sodium bicarbonate (SBC) inhibited in vitro mycelial growth of A. alternata, Fusarium spp. and R. stolonifer. SBC action was fungistatic rather than fungicidal. Coating commercially harvested ‘Galia’ and ‘Ein-Dor’ melons with wax containing 2% SBC reduced decay incidence after storage and shelf life simulation by four to seven-fold, to a commercially acceptable level of 6–7%, compared to untreated or waxed-treated controls. This treatment also maintained the fresh and blemish-free appearance of the fruit at harvest. Higher concentrations of SBC (3%) were phytotoxic and significantly reduced general fruit appearance. A trial shipment by sea transport to Europe demonstrated that 2% SBC incorporated into a wax coating maintained the marketability of ‘Galia’ melon fruits compared to that of untreated fruit. SBC can be an alternative biocide to the fungicide imazalil, thus eliminating unwanted residues on melon fruits.
Control of citrus blue mold, caused by Penicillium italicum, was evaluated on artificially inoculated oranges immersed in water at up to 75°C for 150 s; in 2 to 4% sodium carbonate (wt/vol) at 20 or 45°C for 60 or 150 s; or in 1 to 4% sodium bicarbonate at room temperature for 150 s, followed by storage at 20°C for 7 days. Hot water controlled blue mold at 50 to 55°C, temperatures near those that injured fruit, and its effectiveness declined after 14 days of storage. Sodium carbonate and sodium bicarbonate were superior to hot water. Temperature of sodium carbonate solutions influenced effectiveness more than concentration or immersion period. Sodium carbonate applied for 150 s at 45°C at 3 or 4% reduced decay more than 90%. Sodium bicarbonate applied at room temperature at 2 to 4% reduced blue mold by more than 50%, while 1% was ineffective. In another set of experiments, treatments of sodium bicarbonate at room temperature, sodium carbonate at 45°C, and hot water at 45°C reduced blue mold incidence on artificially inoculated oranges to 6, 14, and 27%, respectively, after 3 weeks of storage at 3°C. These treatments reduced green mold incidence to 6, 1, and 12%, respectively, while incidence among controls of both molds was about 100%. When reexamined 5 weeks later, the effectiveness of all, particularly hot water, declined. In conclusion, efficacy of hot water, sodium carbonate, and sodium bicarbonate treatments against blue mold compared to that against green mold was similar after storage at 20°C but proved inferior during long-term cold storage.
Smilanick, J. L., Margosan, D. A., Mlikota, F., Usall, J., and Michael, I. F. 1999. Control of citrus green mold by carbonate and bicarbonate salts and the influence of commercial posthar- vest practices on their efficacy. Plant Dis. 83: 139-145. The toxicity to Penicillium digitatum and practical use of carbonate and bicarbonate salts to control green mold were determined. The effective dose (ED 50) concentrations to inhibit the germination of P. digitatum spores of sodium carbonate (SC), potassium carbonate, sodium bicarbonate (SBC), ammonium bicarbonate, and potassium bicarbonate were 5.0, 6.2, 14.1, 16.4, and 33.4 mM, respectively. All were fungistatic b ecause spores removed from the solu- tions germinated in potato dextrose broth. SC and SBC were equal and superior to the other salts for control of green mold on lemons and oranges inoculated 24 h before treatment. When sodium content and high pH must be minimized, SBC could replace SC. Furthermore, because a higher proportion of NaOCl would be present in the active hypochlorous acid at the lower pH of SBC compared to SC, sanitation of the SBC solution should be easier to maintain. NaOCl (200 µg/ml) added to SBC at pH 7.5 improved green mold control. Rinse water as high as 50 ml per fruit applied after SC did not reduce its effectiveness; however, high-pressure water cleaning after SC did. Conversely, high-pressure water cleaning of fruit before SC improved control of green mold. The risk of injury to fruit posed by SC treatment was determined by immersing oranges for 1 min in 3% (wt/vol) SC at 28, 33, 44, 50, 56, or 61°C ( ±1°C) and followed by stor- age for 3 weeks at 10°C. Rind injuries occurred only after treatment at 56 and 61°C. The risk of injury is low because these temperatures exceed that needed for control of green mold. SC was compatible with subsequent imazalil and biological control treatments.
A standardized reference method for dermatophyte in vitro susceptibility testing is lacking. In a previous study, Norris et al. (H. A. Norris, B. E. Elewski, and M. A. Ghannoum, J. Am. Acad. Dermatol. 40(6, part 2):S9-S13) established the optimal medium and other growth variables. However, the earlier study did not address two issues: (i) selection of an optimal medium for conidial formation by dermatophytes and (ii) validation of the method with a large number of dermatophytes. The present study addresses these two points. To select which agar medium best supported conidial growth, representative isolates of dermatophytes were grown on different agars. Preliminary experiments showed that only oatmeal cereal agar supported the production of conidia by Trichophyton rubrum. We tested the abilities of 251 T. rubrum isolates to form conidia using three different cereal agars and potato dextrose agar. Overall, oatmeal cereal and rice agar media were comparable in their abilities to support T. rubrum conidial growth. Next, we used the oatmeal cereal agar for conidial formation along with the optimal conditions for dermatophyte susceptibility testing proposed by Norris et al. and determined the antifungal susceptibilities of 217 dermatophytes to fluconazole, griseofulvin, itraconazole, and terbinafine. Relative to the other agents tested, terbinafine possessed the highest antifungal activity against all of the dermatophytes. The mean +/- standard error of the mean MICs of fluconazole, itraconazole, terbinafine, and griseofulvin were 2.07 +/- 0.29, 0.13 +/- 0.01, 0.002 +/- 0.0003, and 0.71 +/- 0.05 microgram/ml, respectively. This study is the first step in the identification of optimal conditions that could be used for the standardization of the antifungal susceptibility testing method for dermatophytes. Inter- and intralaboratory agreement as well as clinical correlations need to be established.
Fungal colonies expand through apically extending peripheral hyphae. These long and relatively unbranched leaders leave behind cells that show a higher degree of branching and lower growth rates. Towards the centre of the colony, quiescent, but viable cells sustain processes such as transport of water, solutes and organelles, and support the concerted genesis of specialized reproductive structures. A survey of chemical signals controlling changes in hyphal growth and branching of Aspergillus nidulans in solid minimal medium revealed that progressive accumulation of bicarbonate from the periphery to the centre of the colony effected a dual modulation of both parameters. At areas immediately behind the periphery, bicarbonate induced progressive branching without a significant change in the specific growth rate. At distal and central regions, increased branching was accompanied by progressive inhibition of the specific growth rate. The results provide new evidence that chemical cues participate in the control of colony morphology and function, which are likely to vary with changing environmental conditions.
Candida albicans produced a karatinolytic proteinase (KPase) or C. albicans producing proteinase (CAPP), a proposed new term for this enzyme, and Trichophyton mentagrophytes also produced KPase when cultivated in liquid medium containing human stratum corneum (HSC) as the nitrogen source, but were unable to do so when cultivated in sabouraud dextrose broth. Purified KPase from the culture supernatants of C. albicans had a molecular weight of 42,000 and an optimum pH at 4.0. The KPase was found to belong to the carboxyl proteinases group and its activity was strongly inhibited by pepstatin. Both fungi were able to grow by secreting KPase which digested HSC for nutrients. KPase from both fungi had high activity in each optimum pH, such as weakly acidic pH on C. albicans and neutral pH on T. mentagrophytes to adapt their surrounding environment by changing the environmental pH into their own optimum pH.
The National Committee for Clinical Laboratory Standards (NCCLS) M38-A standard for the susceptibility testing of conidium-forming
filamentous fungi does not explicitly address the testing of dermatophytes. This multicenter study, involving six laboratories,
investigated the MIC reproducibility of seven antifungal agents tested against 25 dermatophyte isolates (5 blinded pairs of
five dermatophyte species per site for a total of 300 tests), using the method of dermatophyte testing developed at the Center
for Medical Mycology, Cleveland, Ohio. The dermatophytes tested included Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis. Seven antifungals with activity against dermatophytes were tested, including ciclopirox, fluconazole, griseofulvin, itraconazole,
posaconazole, terbinafine, and voriconazole. Interlaboratory MICs for all isolates were in 92 to 100% agreement at a visual
endpoint reading of 50% inhibition as compared to the growth control and 88 to 99% agreement at a visual endpoint reading
of 80% inhibition as compared to the growth control. Intralaboratory MICs between blinded pairs were in 97% agreement at a
visual endpoint reading of 50% inhibition as compared to the growth control and 96% agreement at a visual endpoint reading
of 80% inhibition as compared to the growth control. Data from this study support consideration of this method as an amendment
to the NCCLS M38-A standard for the testing of dermatophytes.
Fungicide resistance in Botrytis cinerea has caused increased concerns about losses due to gray mold on many important agricultural and horticultural crops. Since bicarbonates have been reported to be an effective control of powdery mildew on greenhouse roses, the purpose of this research was to determine the effectiveness of bicarbonates against B. cinerea. Assessments were made of in vitro fungal colony growth in response to ammonium, potassium, and sodium bicarbonates. Bicarbonates inhibited colony growth at concentrations as low as 20 mM. In addition, comparisons of several ammonium, potassium, and sodium salts were conducted to determine whether cation or anion is the active moiety. Although the bicarbonate anion primarily affected growth, the ammonium cation also contributed greatly to fungal growth inhibition. With the exception of dibasic phosphate, only salts with high pK(a), values or that are reducing agents, or both, decreased colony growth. The effect of pH on B. cinerea was then examined. Since bicarbonate anion concentration is related to pH, this parameter was examined in combination with several salts to separate pH effects from bicarbonate effects. As pH increased from 7.0 to 8.5, colony growth decreased with bicarbonates and phosphates, but not with ammonium sulfate. Since bicarbonates and phosphates decreased colony growth more than could be accounted for from pH alone, and since both have buffering characteristics, buffering capacity was examined and found to decrease colony growth but not as much as bicarbonate. Therefore, bicarbonates control B. cinerea colony growth in vitro, and both pH and buffering capacity contribute to, but are not solely responsible for, growth inhibition.
Sodium bicarbonate (SB) inhibited the growth of bacteria and yeasts in agar media model systems under certain conditions. Escherichia coli, Lactobacillus plantarum, Staphylococcus aureus, and Pseudomonas aeruginosa aerobic plate counts were reduced 10,000-fold by 0.12M (1% w/v) SB. Saccharomyces cerevisiae and Hansenula wingei were more sensitive; counts were reduced 100,000-fold by 0.06M SB. Potassium bicarbonate was equally inhibitory, but equimolar sodium chloride had no effect, ruling out osmotic- and sodium-mediated mechanisms of inhibition. The bicarbonate ion was identified as the probable cause of SB-mediated inhibition although, in some cases, pH elevation played a significant role.
Oral candidiasis is a major problem in developing countries where antiretroviral therapy is available to a small percentage of the infected population. HIV patients are prone to xerostomia and predisposed to Candida infection. Preventing oral candidiasis is better than the frequent use of antifungals that may lead to the development of drug resistance. This study investigated the ability of commercial mouth rinses and sodium bicarbonate to reduce salivary Candida and to improve the saliva flow of HIV-positive patients. One hundred fifty HIV patients without oral candidiasis were examined for oral lesions initially and after 2, 4, and 12 weeks. Unstimulated saliva was collected; the volume was measured and cultured for yeasts. Subjects were provided with mouth rinses containing either benzydamine hydrochloride, benzydamine hydrochloride with chlorhexidine gluconate, triclosan with sodium fluoride, 5% sodium bicarbonate, or placebo and asked to rinse twice daily for 12 weeks. The effect of the mouth rinses and placebo on Candida counts and saliva flow was analyzed using analysis of variance (ANOVA). A total of 108 patients completed the trial, 35 missed appointments, 4 died, 2 developed oral candidiasis, and 1 herpetic lesion. Triclosan/fluoride decreased the Candida count more than the placebo (p = 0.005) while chlorhexidine/benzydamine hydrochloride (p = 0.001) and triclosan/fluoride mouthrinses (p = 0.002) increased the salivary flow during the initial 4 weeks. The most effective mouth rinse triclosan/fluoride decreased oral Candida counts and increased saliva flow. Studies are needed to determine the efficacy of these mouth rinses for the long-term prevention of clinical oral candidiasis in adult HIV-positive patients.
Nondermatophyte onychomycosis account for 2% to 12% of all nail fungal infections and can be caused by a wide range of fungi, mainly Scopulariopsis brevicaulis, Aspergillus versicolor, A. flavus, A. niger, A. fumigatus, Fusarium solani, F. oxysporum and Scytalidium spp. Among the predisposing factors are footwear, hyperhidrosis, local trauma, peripheral circulatory disease, and immunosuppression. These nondermatophyte fungi lack the keratinolytic capacity of dermatophytes, but they still can infect alone or in combination with the latter. Because most are considered laboratory contaminants, special criteria have been created for the correct diagnosis of nondermatophyte onychomycosis. The etiologic agent does not determine the clinical pattern of nail invasion, but superficial onychomycosis is frequently observed; leukonychia and melanonychia can also be clinical manifestations.
Onychomycosis is a frequent nail disease caused by dermatophytes, yeasts, and nondermatophyte molds. Trichophyton rubrum, T mentagrophytes, and Epidermophyton floccosum are the most common etiologic agents worldwide. Candida spp are the most frequent among the yeasts. Diagnosis is corroborated by direct microscopic examination, culture, and histomycology with periodic acid-Schiff stain. Other new methods of diagnosis are discussed. Treatment is based on oral antifungals: terbinafine, itraconazole, and fluconazole, including other emerging triazole drugs. Therapeutic outcome with ciclopirox and amorolfine lacquers alone and combined with systemic therapy are also reviewed, as well as the new nail enhancers and physical and chemical removal of the diseased nails.
The virulence of Candida species depends on many environmental conditions, including extracellular pH and concentration of alkali metal cations. Tests of the tolerance/sensitivity of four pathogenic Candida species (C. albicans, C. dubliniensis, C. glabrata, and C. parapsilosis) to alkali metal cations under various growth conditions revealed significant differences among these species. Though all of them can be classified as rather osmotolerant yeast species, they exhibit different levels of tolerance to different salts. C. parapsilosis and C. albicans are the most salt-tolerant in general; C. dubliniensis is the least tolerant on rich YPD media and C. glabrata on acidic (pH 3.5) minimal YNB medium. C. dubliniensis is relatively salt-sensitive in spite of its ability to maintain as high intracellular K(+)/Na(+) ratio as its highly salt-tolerant relative C. albicans. On the other hand, C. parapsilosis can grow in the presence of very high external NaCl concentrations in spite of its high intracellular Na(+) concentrations (and thus lower K(+)/Na(+) ratio) and thus resembles salt-tolerant (halophilic) Debaryomyces hansenii.
The efficacy of thiabendazole (TBZ) to control postharvest decay caused by Penicillium digitatum of citrus fruit can be enhanced by co-application with sodium bicarbonate (SBC) and/or heat treatment. The impact of these treatments was investigated in citrus fruit, as a function of TBZ and SBC concentration and temperature, and were related to the amount of TBZ residues in fruit (total residues), in fruit surface, in the cuticular wax, and in the inner fruit. The residue levels of TBZ were determined in 'Valencia' oranges following a 1 min dip in an aqueous mixture of SBC at 0.5, 1, or 2 wt %/vol and TBZ at 600 or 400 mg/L (active ingredient, a.i.) at 20 or 40 degrees C and after 0 and 20 days at 17 degrees C and 90% relative humidity. The influence of SBC and heat on the TBZ residue concentration on the fruit surface, in cuticular wax, and on the inner cuticle tissue was determined in 'Salustiana' oranges after a 1 or 3 min dip in TBZ alone at 600 mg/L and 20 or 50 degrees C or for 1 min in TBZ at 600 mg/L and SBC at 2% and 20 degrees C. The efficacy of heat treatments with water, SBC, and TBZ, applied separately or in combination, was investigated on artificially inoculated 'Nova' mandarins and 'Valencia' oranges for the control of postharvest green mold caused by a TBZ-sensitive (TBZ-s) or TBZ-resistant (TBZ-r) isolate of P. digitatum. The residue levels of TBZ in fruit, evaluated as total residues, were not affected by the co-application of SBC in most samples. While TBZ residues in the fruit surface were not significantly affected by the dip temperature or by co-application of SBC, the rates of diffusion and penetration of TBZ into cuticular wax markedly increased in the presence of SBC or when TBZ was applied in combination with heat. TBZ residues in the inner tissue of fruits treated at 20 degrees C were not dependent upon the dip time or by the presence of SBC and were similar to those found in fruit treated with TBZ at 50 degrees C for 1 min, whereas significantly higher values were recorded in samples treated with TBZ at 50 degrees C for 3 min. When TBZ at 600 mg/L and 20 degrees C was applied in the presence of SBC at concentrations of 1-2 or 0.5-2%, it effectively reduced decay caused by the TBZ-resistant isolate of green mold in 'Nova' mandarins and 'Valencia' oranges. This treatment was also significantly more effective than TBZ alone to control green mold caused by a TBZ-s isolate in 'Valencia' oranges. The combination with SBC and mild heat (40 degrees C) and TBZ at 400 mg/L generally improved the control of a TBZ-r isolate of green mold with respect to the combined treatment at 20 degrees C. TBZ efficacy was also improved when applied at reduced rates (200 mg/L) and 50 degrees C, significantly suppressing green mold caused by a TBZ-s isolate of P. digitatum and effectively controlling a TBZ-r isolate. The rate of weight loss of 'Valencia' oranges was significantly increased by SBC treatment and was positively dependent upon the concentration of SBC used in the treatment, while the temperature of the treatment solution had little influence on later weight loss.
In this study we examined the mechanism by which ammonium bicarbonate inhibits mycotoxigenic fungi. Elevated extracellular pH, alone, was not responsible for the antifungal activity. Although conidia of Penicillium griseofulvum and Fusarium graminearum had internal pH (pHi) values as high as 8.0 in buffer at an external pH (pHo) of 9.5, their viability was not markedly affected. The pHi values from conidia equilibrated in glycine-NaOH-buffered treatments without ammonium bicarbonate or ammonium sulfate were similar to values obtained from buffered treatments containing the ammonium salts. Thus, inhibition did not appear to be directly related to increased pHi. Ammonium sulfate in buffered media at pH greater than or equal to 8.7 was as inhibitory as ammonium bicarbonate, but was completely ineffective at pH less than or equal to 7.8. The hypothesis that free ammonia caused the fungal inhibition was tested by using ammonium sulfate as a model for ammonium bicarbonate. Viability, expressed as log CFU/ml, and percent germination of P. griseofulvum and F. graminearum decreased dramatically as the free ammonia concentration increased. Germination rate ratios (the germination rate in buffered ammonium sulfate divided by the germination rate in buffer alone) decreased linearly as the free ammonia concentration increased, further establishing NH3 as the toxic agent. Ammonium bicarbonate inhibits fungi because the bicarbonate anion supplies the alkalinity necessary to establish an antifungal concentration of free ammonia.
The ability of sodium bicarbonate to inhibit growth of Saccharomyces cerevisiae and Hansenula wingei in apple juice was investigated. Sodium bicarbonate at concentrations of 0.06, 0.12, and 0.24 M was added to pasteurized apple juice that was then inoculated with 10(3) or 10(5) cfu/ml of either yeast. Growth of both yeasts was inhibited by 0.12 M sodium bicarbonate when incubation was at 4 degrees C; 0.24 M sodium bicarbonate caused a slow die off of yeast. At 18 degrees C, H. wingei became more sensitive and died in the presence of 0.12 M sodium bicarbonate, but S. cerevisiae became resistant to 0.24 M sodium bicarbonate. These results could not be attributed to bicarbonate-induced pH elevation or sodium. Potassium and ammonium bicarbonate were also inhibitory, implicating bicarbonate ion as the antimicrobial agent.
The potential of sodium bicarbonate to inhibit growth of and aflatoxin synthesis by Aspergillus parasiticus was examined in Czapek's agar (CA), a medium in which fluorescence under UV light indicates aflatoxin production. Incorporation of sodium bicarbonate (SB) into CA at 0.011, 0.022, and 0.033 mol% reduced cell viability 63-, 10(3)-, and greater than 10(7)-fold, respectively. Colonies resulting from surviving cells did not fluoresce under UV light, but thin-layer chromatography analysis of culture extracts detected aflatoxins. Potassium bicarbonate (KB) at 0.011 and 0.022 mol% produced inhibitory effects similar to those of SB, but NaCl and silica had no effect. After 7 days, control cultures had the normal aflatoxin distribution (B1 greater than G1 greater than B2 greater than G2), but this distribution shifted to B2 greater than B1 approximately equal to G2 greater than G1 during prolonged incubation. Cultures supplemented with SB and KB contained mostly aflatoxins B1 and G1 after 28 days. Both SB and KB raised the pH of CA to 7.5 to 8.5 at the time of growth. Culture growth on CA adjusted to pH 7.5 to 8.5 with NaOH was not inhibited but exhibited reduced fluorescence and elevated levels of aflatoxins B1 and G1. Thus, while bicarbonate inhibition of growth could not be attributed to pH elevation, the lack of culture fluorescence on CA-SB and CA-KB and the altered aflatoxin distribution were caused by the ability of SB and KB to elevate pH.
Superficial fungal infections of the skin are a common problem in childhood. Infections of the scalp are especially important because they frequently cause hair loss which, if left untreated, may be permanent. In immunosuppressed or debilitated patients, the superficial fungi can cause considerable morbidity and even mortality. There have been a number of new developments since this subject was last reviewed in the Pediatric Clinics. This article will deal with the three main types of superficial fungal infections: the dermatophytoses, tinea versicolor, and Candidal infections.
The NHA1 gene of Saccharomyces cerevisiae, transcribed into a 3.5 kb mRNA, encodes a protein mediating Na+ and K+ efflux through the plasma membrane that is required for alkali cation tolerance at acidic pH. Deletion of the gene in a wild-type strain resulted in higher sensitivity to both K+ and Na+ at acidic pH. Measurements of cation loss in strains carrying deleted or overexpressed alleles of NHA1 demonstrated its role in K+ and Na+ efflux. In addition, high K+ and Na+ efflux observed upon alkalinization of the cytoplasm implies a role of Nha1p in the regulation of intracellular pH. Moreover, the overexpression of ENA1 and NHA1 genes in an ena1-4 delta-nha1 delta strain showed that the Nha1 alkalication antiporter is responsible for growth on high concentrations of KCl and NaCl at acidic pH, and Ena alkali-cation ATPases are necessary at higher pH values. Both systems have a complementary action to maintain the intracellular steady-state concentration of K+ and Na+.
The survival of Lactobacillus curvatus LTH 1174 (bac ) and (bac ) in combination with Escherichia coli LTH 1600 or Listeria innocua DSM20649 during transit through a dynamic model of the human stomach and small intestine (GIT model) was studied. Furthermore, we determined the digestion of curvacin A during gastro-intestinal transit and the effect of this bacteriocin on microbial survival. Lb. curvatus is rapidly killed in the gastric compartment at pH < 2.0, and less than 0.01% of the cells delivered to the small intestinal compartments were recovered from the ileal compartment of the model. Meat exerted a protective effect against the lethal action of bile against Lb. curvatus. The sensitivity of E. coli to acid depended on the aeration of the preculture and decreased in the order anaerobic > strongly agitated > agitated. Lactic acid and curvacin A enhanced the lethal effect of low pH on E. coli. Accordingly, cells from strongly agitated cultures were killed faster in the gastric compartment of the GIT model than those from agitated cultures, and inactivation was accelerated in the presence of curvacin A. E. coli tolerated the bile concentrations prevailing in the small intestinal compartments of the model. The survival of Listeria innocua in the GIT model was comparable to that of Lb. curvatus. The curvacin A produced by Lb. curvatus LTH1174 (bac+) killed > 90% of the L. innocua within 10 min after mixing of the cultures. Curvacin A was not degraded in the the gastric compartment, and could be detected in the ileal compartment during the first 180 min upon addition of the meal.
The constant input of chemical fungicides against foliar diseases in glasshouse crops has instigated research on alternative control substances. Various salts have been mentioned in the literature and we have tested several bicarbonates, sulphates and phosphates against powdery mildew fungi in cucumber, tomato, sweet pepper and rose and against Bremia lactucae in lettuce. The experiments were run according to EPPO guidelines for efficacy in glasshouses of Applied Plant Research (PPO). Plants were sprayed weekly and disease and yield were assessed. In cucumber, NaHCO3, KHCO3, MgSO4 and MnSO4 all reduced powdery mildew significantly, with MnSO4 as the most effective agent. In tomato, MgSO4, MnSO4 and KH2PO4 all reduced powdery mildew by approx. 40% whereas NaHCO3 and KHCO3 gave approx. 95% control. In pepper, NaHCO3 controlled Leveillula taurica by 50-90% compared to the untreated control. In rose, the efficacy of KH2PO4, MnSO4, MgSO4, NaHCO3 and KHCO3 against powdery mildew differed between cultivars. In general, the bicarbonates were the most effective compounds. In lettuce, NaHCO3 reduced Bremia severity by 70 to 80%. The conclusion of this range of experiments is that especially bicarbonates can be a good alternative for control of foliar fungal diseases in glasshouse crops. The effective concentration is not causing any symptoms of phytotoxicity, provided that spraying is not done at high irradiation conditions. Bicarbonates have been submitted for the Dutch list of exceptions on the Pesticide Law.
Superficial fungal infections arise from a pathogen that is restricted to the stratum corneum, with little or no tissue reaction. In this Seminar, three types of infection will be covered: tinea versicolor, piedra, and tinea nigra. Tinea versicolor is common worldwide and is caused by Malassezia spp, which are human saprophytes that sometimes switch from yeast to pathogenic mycelial form. Malassezia furfur, Malassezia globosa, and Malassezia sympodialis are most closely linked to tinea versicolor. White and black piedra are both common in tropical regions of the world; white piedra is also endemic in temperate climates. Black piedra is caused by Piedraia hortae; white piedra is due to pathogenic species of the Trichosporon genus. Tinea nigra is also common in tropical areas and has been confused with melanoma.
For centuries, medicated baths have been one of the first lines of treatment for psoriasis. Even today, with sophisticated immunosuppressive treatments available, Dead Sea salts and spa waters are recognized to be beneficial in the management of psoriatic patients.
To assess statistically the efficacy of sodium bicarbonate (NaHCO3) baths in psoriasis patients. Methods: Thirty-one patients with mild-moderate psoriasis were admitted to this study; Nineteen patients were treated with sodium bicarbonate baths and compared with twelve patients who were administered a placebo. Assessments were made on days 0 and 21.
Almost all patients who used NaHCO3 reported a statistically valuable improvement. NaHCO3 baths reduced itchiness and irritation; in general, the patients themselves recognized a beneficial impact on their psoriasis, so much so that they have continued to bathe in NaHCO3 even after the end of the study.
We maintain that even with sophisticated immunosuppressive and highly specific anti-cytokine and anti-chemokines treatments available for the treatment of psoriasis, an older and often forgotten treatment can still play a role.
The introduction of systemic antifungal drugs which act upon different targets is the main issue of the in vivo antifungal resistance control. Different factors, such as growth curve phase, quality of the specimen, quantity of the inoculum, temperature, pH, culture medium composition, incubation duration and solvent, are believed important factors affecting minimum inhibitory concentration (MIC) value to most of the antifungal agents. We assayed an in vitro susceptibility test with 40 isolates of dermatophytes: Microsporum canis, Trichophyton rubrum, Trichophyton mentagrophytes and Epidermophyton floccosum against griseofulvin, fluconazole, itraconazole and terbinafine, using the guidelines of the M38-P document approved by the NCCLS. We determined the growth curves, to estimate the specific growth rate (mu max) and the generation time (G) of each dermatophyte, using dry weight and spectrophotometry methods. We demonstrate that, at 192 h, all fungi tested had a constant growth curve and we considered this as the optimal time for MIC determination. Terbinafine, griseofulvin and itraconazole possessed the highest antifungal activity against the four groups of dermatophytes studied. Fluconazole demonstrated no efficacy. Our MIC results differ from other authors and this difference is due to the timing of the MIC determination based on the growth curve of each fungi tested.
Amphotericin B and nystatin are two polyene antibiotics that are potent antifungal agents. These drugs are active against most pathogenic fungi like Aspergillus and Candida. Mouthrinses containing these drugs are used for preventive and curative treatment of fungal infections like oral candidiasis, which can cause multiple diseases in cancer patients. Because there were no marketed antifungal mouthrinses available, their preparations were performed at the hospital and town pharmacies. To date, there are no data available on the stability of both these drugs in the form of mouthrinses. Therefore, each mouthrinse had to be prepared extemporaneously. The aim of this study was to investigate the stability of amphotericin B (Fungizone) and nystatin (Mycostatine) in the form of mouthrinses containing 1.4% sodium hydrogen carbonate. The stability of these solutions was tested at different temperatures (4-37 degrees C) with or without electric- or sunlight exposure and in two types of containers (glass and polypropylene) over a 15-day period. The admixtures were also monitored for colour change and pH. Amphotericin B and nystatin were quantified by high-performance liquid chromatography. At 4 degrees C, amphotericin B and nystatin were stable for 15 days in polypropylene. When stored in polypropylene at room temperature, with or without light protection, amphotericin B and nystatin were stable for 3 and 4 days, respectively.
Metal complexation is a key mediator or modifier of enzyme structure and function. In addition to divalent and polyvalent metals, group IA metals Na+ and K+ play important and specific roles that assist function of biological macromolecules. We examine the diversity of monovalent cation (M+)-activated enzymes by first comparing coordination in small molecules followed by a discussion of theoretical and practical aspects. Select examples of enzymes that utilize M+ as a cofactor (type I) or allosteric effector (type II) illustrate the structural basis of activation by Na+ and K+, along with unexpected connections with ion transporters. Kinetic expressions are derived for the analysis of type I and type II activation. In conclusion, we address evolutionary implications of Na+ binding in the trypsin-like proteases of vertebrate blood coagulation. From this analysis, M+ complexation has the potential to be an efficient regulator of enzyme catalysis and stability and offers novel strategies for protein engineering to improve enzyme function.
Clinical Laboratory Standards Institute (CLSI) Method for antifungal disk diffusion susceptibility testing in yeasts, approved guideline
- A Wayne
- O Welsh
- L Vera-Cabrera
- Welsh E Onychomycosis
Welsh O, Vera-Cabrera L, Welsh E. Onychomycosis. Clin
Dermatol. 2010;28:151-9.
Factors affecting the synergy of thiabendazole, sodium bicarbonate, and heat to control postharvest green mold of citrus fruit
- M Schirra
- D 'aquino
- S Palma
Schirra M, D'Aquino S, Palma A, et al. Factors affecting the
synergy of thiabendazole, sodium bicarbonate, and heat to
control postharvest green mold of citrus fruit. J Agric Food
Chem. 2008;56:10793-8.
Antifungal susceptibility testing of dermatophytes: establishing a medium for inducing conidial growth and evaluation of susceptibility of clinical isolates
- C J Jessup
- J Warner
- N Isham
- CJ Jessup
The Nha1 antiporter of Saccharomyces cerevisiae mediates sodium and potassium efflux
- M A Banuelos
- H Sychrova
- C Bleykasten-Grosshans
- MA Banuelos